Homologous recombination repair gene mutation (HRRm) testing patterns and treatment selection from a real-world cohort of patients with metastatic castration-resistant prostate cancer (mCRPC).

Abstract

210 Background: Routine germline and somatic testing is recommended by professional guidelines as standard of care for all mCRPC patients since the approvals of poly ADP ribose polymerase inhibitors (PARPi) for treatment in those with tumors harboring select HRRm. Yet, analyses suggest that many mCRPC patients are not offered testing and thus patients with HRRm+ tumors may not have the shared decision-making opportunity to consider PARPi therapy. We reviewed HRR testing and treatment patterns within a real-world cohort of mCRPC patients to identify potential clinical practice gaps. Methods: The IntegraConnect – Precision Q Database that includes electronic, practice management and payer data from 500 US sites of care was utilized to select a de-identified real-world cohort of newly diagnosed and actively treated mCRPC patients (excluding those with lymph node only metastasis) between 1/1/2020 – 12/31/2021. Patient charts were manually reviewed by medical curators to extract data including frequency and timing of germline and somatic testing for HRRm, testing modality (tissue or liquid biopsy), results of HRRm testing, and the use of PARPi in the HRRm+ patient cohort. Results: A total of 996 mCRPC patients met criteria with 93% managed by community oncologists, 6% community urologists, and 1% academic oncologists. 59.2% (n=590) received testing for HRRm (19.8% germline (n=117); 59.8% somatic (n=353); 4.1% (n=24) germline + somatic; 16.3% (n=96) unknown) with testing rates increasing after PARPi approval: 15% between 1/1/2020 – 5/31/2020; 23% between 6/1/2020 – 9/30/2020; 62% between 10/1/2020 – 12/31/2021. The vast majority (64%) were tested after receiving mCRPC treatment, with 48% tested after failure on first line therapy. Somatic tissue testing was the predominant testing modality over liquid biopsy and germline testing. 31.7% (n=187) of tested patients were HRRm+ (11.2% germline (n=21); 73.8% somatic (n=138); 2.1% (n=4) germline + somatic; 12.8% (n=24) unknown), though not all tests utilized included the 14 HRR genes in the olaparib approval. BRCA2, ATM, CHEK2, and CDK12 HRRm were most commonly detected with a higher frequency of ATM and CHEK2 mutations seen in liquid biopsies. Of the mCRPC patients who were HRRm+, 66.8% (n=125) received PARPi. Conclusions: In this real-world analysis, 40.8% of mCRPC patients did not receive germline or somatic testing while 33.2% of HRRm+ patients did not receive PARPi. Optimizing germline and somatic testing for mCRPC is a significant unmet need, which negatively impacts therapeutic offerings.